6i5i - Revision history

OCA at 11:47, 24 January 2024

OCA — Wed, 24 Jan 2024 11:47:18 GMT

←Older revision		Revision as of 11:47, 24 January 2024
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	==Crystal structure of CLK1 in complexed with furo[3,2-b]pyridine compound 12h==		==Crystal structure of CLK1 in complexed with furo[3,2-b]pyridine compound 12h==
-	<StructureSection load='6i5i' size='340' side='right' caption='[[6i5i]], [[Resolution\|resolution]] 1.60Å' scene=''>	+	<StructureSection load='6i5i' size='340' side='right'caption='[[6i5i]], [[Resolution\|resolution]] 1.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6i5i]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I5I OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6I5I FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6i5i]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I5I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6I5I FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=H3E:5-(1-methylpyrazol-4-yl)-3-[1-(phenylmethyl)pyrazol-4-yl]furo[3,2-b]pyridine'>H3E</scene~~></td></tr>~~	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.6Å</td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dual-specificity_kinase Dual-specificity kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.12.1 2.7.12.1] </span></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=H3E:5-(1-methylpyrazol-4-yl)-3-[1-(phenylmethyl)pyrazol-4-yl]furo[3,2-b]pyridine'>H3E</scene></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6i5i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i5i OCA], [~~http~~://pdbe.org/6i5i PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6i5i RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6i5i PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6i5i ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6i5i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i5i OCA], [https://pdbe.org/6i5i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6i5i RCSB], [https://www.ebi.ac.uk/pdbsum/6i5i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6i5i ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/CLK1_HUMAN CLK1_HUMAN]] Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex and may be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing. Phosphorylates: SRSF1, SRSF3 and PTPN1. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells and adenovirus E1A pre-mRNA.<ref>PMID:10480872</ref> <ref>PMID:19168442</ref>	+	[https://www.uniprot.org/uniprot/CLK1_HUMAN CLK1_HUMAN] Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex and may be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing. Phosphorylates: SRSF1, SRSF3 and PTPN1. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells and adenovirus E1A pre-mRNA.<ref>PMID:10480872</ref> <ref>PMID:19168442</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 6i5i" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6i5i" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Dual specificity protein kinase 3D structures\|Dual specificity protein kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Dual-specificity kinase~~]]	+	[[Category: Homo sapiens]]
-	[[Category: Arrowsmith~~, C H~~]]	+	[[Category: Large Structures]]
-	[[Category: Bountra, C]]	+	[[Category: Arrowsmith CH]]
-	[[Category: Chaikuad, A]]	+	[[Category: Bountra C]]
-	[[Category: Edwards~~, A M~~]]	+	[[Category: Chaikuad A]]
-	[[Category: Knapp, S]]	+	[[Category: Edwards AM]]
-	[[Category: Paruch, K]]	+	[[Category: Knapp S]]
-	~~[[Category: Structural genomic]]~~	+	[[Category: Paruch K]]
-	~~[[Category: Clk]]~~	+
-	~~[[Category: Furopyridine]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Sgc]]~~	+
-	~~[[Category: Splicing kinase]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 06:37, 9 January 2019

OCA — Wed, 09 Jan 2019 06:37:08 GMT

←Older revision		Revision as of 06:37, 9 January 2019
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-	'''Unreleased structure'''

-	~~The entry~~ 6i5i is ~~ON HOLD~~	+	==Crystal structure of CLK1 in complexed with furo[3,2-b]pyridine compound 12h==
		+	<StructureSection load='6i5i' size='340' side='right' caption='[[6i5i]], [[Resolution\|resolution]] 1.60Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6i5i]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I5I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6I5I FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=H3E:5-(1-methylpyrazol-4-yl)-3-[1-(phenylmethyl)pyrazol-4-yl]furo[3,2-b]pyridine'>H3E</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dual-specificity_kinase Dual-specificity kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.12.1 2.7.12.1] </span></td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6i5i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i5i OCA], [http://pdbe.org/6i5i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6i5i RCSB], [http://www.ebi.ac.uk/pdbsum/6i5i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6i5i ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/CLK1_HUMAN CLK1_HUMAN]] Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex and may be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing. Phosphorylates: SRSF1, SRSF3 and PTPN1. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells and adenovirus E1A pre-mRNA.<ref>PMID:10480872</ref> <ref>PMID:19168442</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Reported is the identification of the furo[3,2-b]pyridine core as a novel scaffold for potent and highly selective inhibitors of cdc-like kinases (CLKs) and efficient modulators of the Hedgehog signaling pathway. Initially, a diverse target compound set was prepared by synthetic sequences based on chemoselective metal-mediated couplings, including assembly of the furo[3,2-b]pyridine scaffold by copper-mediated oxidative cyclization. Optimization of the subseries containing 3,5-disubstituted furo[3,2-b]pyridines afforded potent, cell-active, and highly selective inhibitors of CLKs. Profiling of the kinase-inactive subset of 3,5,7-trisubstituted furo[3,2-b]pyridines revealed sub-micromolar modulators of the Hedgehog pathway.

-	~~Authors~~: ~~Chaikuad,~~ A., ~~Arrowsmith~~, ~~C.H.~~, ~~Edwards~~, A.M., ~~Bountra~~, C., ~~Paruch~~, K., ~~Knapp~~, S., ~~Structural Genomics Consortium (SGC)~~	+	Furo[3,2-b]pyridine: A Privileged Scaffold for Highly Selective Kinase Inhibitors and Effective Modulators of the Hedgehog Pathway.,Nemec V, Hylsova M, Maier L, Flegel J, Sievers S, Ziegler S, Schroeder M, Berger BT, Chaikuad A, Valcikova B, Uldrijan S, Drapela S, Soucek K, Waldmann H, Knapp S, Paruch K Angew Chem Int Ed Engl. 2018 Dec 20. doi: 10.1002/anie.201810312. PMID:30569600<ref>PMID:30569600</ref>

-	~~Description: Crystal structure~~ of ~~CLK1 in complexed with furo~~[~~3,2~~-b]~~pyridine compound 12h~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 6i5i" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Dual-specificity kinase]]
		+	[[Category: Arrowsmith, C H]]
		+	[[Category: Bountra, C]]
	[[Category: Chaikuad, A]]		[[Category: Chaikuad, A]]
-	[[Category: ~~Arrowsmith~~, ~~C.H~~]]	+	[[Category: Edwards, A M]]
	[[Category: Knapp, S]]		[[Category: Knapp, S]]
-	[[Category: Edwards, A.M]]
	[[Category: Paruch, K]]		[[Category: Paruch, K]]
-	[[Category: Structural ~~Genomics Consortium (~~Sgc)]]	+	[[Category: Structural genomic]]
-	[[Category: ~~Bountra, C~~]]	+	[[Category: Clk]]
		+	[[Category: Furopyridine]]
		+	[[Category: Inhibitor]]
		+	[[Category: Sgc]]
		+	[[Category: Splicing kinase]]
		+	[[Category: Transferase]]

OCA: Protected "6i5i" [edit=sysop:move=sysop]

OCA — Sun, 02 Dec 2018 18:36:04 GMT

Protected "6i5i" [edit=sysop:move=sysop]

←Older revision

Revision as of 18:36, 2 December 2018

OCA: New page: '''Unreleased structure''' The entry 6i5i is ON HOLD Authors: Chaikuad, A., Arrowsmith, C.H., Edwards, A.M., Bountra, C., Paruch, K., Knapp, S., Structural Genomics Consortium (SGC) De...

OCA — Sun, 02 Dec 2018 18:36:03 GMT

New page: '''Unreleased structure''' The entry 6i5i is ON HOLD Authors: Chaikuad, A., Arrowsmith, C.H., Edwards, A.M., Bountra, C., Paruch, K., Knapp, S., Structural Genomics Consortium (SGC) De...

New page

'''Unreleased structure'''

The entry 6i5i is ON HOLD

Authors: Chaikuad, A., Arrowsmith, C.H., Edwards, A.M., Bountra, C., Paruch, K., Knapp, S., Structural Genomics Consortium (SGC)

Description: Crystal structure of CLK1 in complexed with furo[3,2-b]pyridine compound 12h
[[Category: Unreleased Structures]]
[[Category: Chaikuad, A]]
[[Category: Arrowsmith, C.H]]
[[Category: Knapp, S]]
[[Category: Edwards, A.M]]
[[Category: Paruch, K]]
[[Category: Structural Genomics Consortium (Sgc)]]
[[Category: Bountra, C]]